title: Differential effects of nitroglycerin, trimetazidine, verapamil and SK&F 24260 on venous return as revealed by the open-loop method in the dog.
abstract: To obtain detailed information concerning the effects of different vasodilators on venous return, experiments were carried out on 28 dogs by the use of the open-loop method. Blood from the superior and inferior venae cavae was drained at the level of the tricuspid valve into a reservoir, from which blood was pumped into the right atrium at a constant flow rate. Changes in reservoir volume reflected a total blood shift from the experimental dog and indicated changes in venous return. Drugs were administered into the ascending aorta. Nitroglycerin (1-10 micrograms/kg) decreased systemic blood pressure, total peripheral resistance and venous return but scarcely altered heart rate. Trimetazidine (0.3-3 mg/kg) decreased systemic blood pressure, total peripheral resistance, venous return and heart rate. Verapamil (10-100 micrograms/kg) decreased systemic blood pressure, total peripheral resistance and heart rate, and increased venous return. SK&F 24260 (1-10 micrograms/kg) decreased systemic blood pressure, total peripheral resistance and increased venous return. Only high doses (10-30 micrograms/kg) of SK&F 24260 reduced heart rate. Rigorous measurements of systemic output showed that nitroglycerin (10 micrograms/kg), trimetazidine (3 mg/kg), verapamil (100 micrograms/kg), SK&F 24260 ( 10 micrograms/kg) produced no change in this parameter. SK&F 24260 increased venous return even when sino-aortic baroreceptor reflex was eliminated, ruling out reflex venoconstriction as a possible cause of the increased venous return. The results suggest the following: [1] Vasodilators like SK&F 24260 and verapamil increase venous return by decreasing arterial and/or venous resistance. [2] If the effect which increases venous capacitance prevails over the effect which decreases arterial and/or venous resistance, venous return is reduced as  is the case of nitroglycerin and trimetazidine.
mesh_terms: D000818:Animals; D001810:Blood Volume / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002346:Carotid Sinus / Q000294:innervation; D003714:Denervation; D004095:Dihydropyridines; D004285:Dogs; D006439:Hemodynamics / Q000187:drug effects*; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology; D008722:Methods; D009539:Nicotinic Acids / Q000494:pharmacology*; D005996:Nitroglycerin / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D014292:Trimetazidine / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects; D014684:Venae Cavae / Q000187:drug effects* / Q000502:physiology; D014700:Verapamil / Q000494:pharmacology*
chemical_list: D004095:Dihydropyridines; D006845:Hydrocarbons, Fluorinated; D009539:Nicotinic Acids; D010879:Piperazines; C001040:1,4-dihydro- 2,6-dimethyl-4-(2-(trifluoromethyl)phenyl)-3,5- pyridinedicarboxylic acid diethyl ester; D014700:Verapamil; D005996:Nitroglycerin; D014292:Trimetazidine